Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

A dynamic scale for surgical activity (DYSSA) stratification during the COVID-19 pandemic

Dear Editor, healthcare systems worldwide are facing the “Severe Acute Respiratory Syndrome CoronaVirus 2” (SARS-CoV-2) pandemic which is responsible for the COrona Virus Disease 2019 (COVID-19) 1. It was first identified in China, in December 2019 and it is responsible for the current outbreak (elevated as Public Health Emergency of International Concern and later to pandemic by the World Health Organization) 1. Due to its rapid diffusion, it is probable that confirmed or suspected COVID-19 patients will eventually need of surgery such as non-infected patients. In many centers, the only possible scenarios will be undeferrable emergency or elective surgeries 2,3. The indication for surgery should be individualized and based on a highly accurate diagnosis, multidisciplinary committees decision and considering the hospital and the affected area conditions 4. Where possible, a non-operative approach could be considered if feasible and always evaluating patient’s risk/benefit 4. Due to the important repercussions that the COVID-19 pandemic is causing, it is important to consider the different scenarios that surgeons might face in their hospitals. To provide useful and practical recommendations for surgical teams in the decision-making process, the Spanish Association of Surgery (Asociación Española de Cirujanos – AEC) established a Working Group of experts named “Surgery-AEC-COVID” 5 which developed the Dynamic Scale for Surgical Activity (DYSSA) (Table 1). It includes five phases, based on the feasibility and suitability of performing elective or emergency surgery for each hospital, that detail the progression of the COVID-19 pandemic. It is based on current literature 2-4 and on the cumulative experience from surgeons and centers after analyzing the situation internationally. In order to validate if DYSSA was a useful scale, applicable to reality, a survey was sent to the AEC and to the European Association for Endoscopic Surgeons (EAES) members. DYSSA resulted “adequate” for 86.8% of the AEC members (427 out of 492 answers) and for 89.1% of the EAES members (271 out of 304 answers) who responded to the survey. Several guidelines are useful for the general management of patients 2-4, however, the aim of the DYSSA is to provide a dynamic classification of the situation of each hospital involved in the pandemic, to be able to help surgeons in the decision-making process, both during the expansion or the restoration of the SARS-CoV-2 infection, and to optimize the available resources. The classification in phases is based on the percentage of hospitalized COVID-19 patients, with detailed recommendations associated with each phase. DYSSA allows addressing patients to the most appropriate hospital in case of resources centralization and to sort patients in the most appropriate hospitals according to the planned surgical strategy at a regional level. In our opinion, DYSSA is a valuable and useful tool to classify scenarios depending on the hospital global situation and to guide surgeons in the prioritization of the operations to perform. It is crucial to highlight that the current pandemic is an unexpected situation that rapidly and continuously evolves, so new and different solutions will have to be considered dynamically

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14,391 patients,8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%,p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p &lt; 0.0001), and cancer-specific survival (p &lt; 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Plant Epigenetic Mechanisms in Response to Biotic Stress

The environment changes faster than the ability of genetic recombination to generate natural genetic diversity. In this context, epigenetic regulation of gene expression has the potential to provide organisms with an alternative mechanism for phenotypic variation by controlling the extent of plasticity that can be achieved in response to environmental changes. There is now substantial evidence suggesting roles for epigenetic regulation of several different aspects of the plant response to biotic stress. At the basic level of gene expression, posttranscriptional gene silencing mediated by small RNAs and chromatin remodelling controlling transcriptional gene silencing are essential for the induced resistance responses activated during pest and pathogen attack. Beyond this, there is also evidence that histone modifications and DNA methylation are associated with immune memory, or defence priming, such as systemic acquired resistance (SAR). In addition, recent evidence indicates that epigenetic modifications can also generate longer-term defence priming responses that can be inherited across generations. In this chapter, we will discuss the roles of epigenetics in these different modes of biotic stress resistance, and suggest ways in which we may in the future be able to exploit epigenetic systems for crop protection

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC